Treatment of Human Plague: A Systematic Review of Published Aggregate Data on Antimicrobial Efficacy, 1939-2019.

BACKGROUND: Plague, caused by the bacterium Yersinia pestis, has killed millions in historic pandemics and continues to cause sporadic outbreaks. Numerous antimicrobials are considered effective for treating plague; however, well-defined information on the relative efficacy of various treatments is lacking. We conducted a systematic review of published data on antimicrobial treatment of plague reported in aggregate. METHODS: We searched databases including Embase, Medline, CINAHL, Cochrane Library, and others for publications with terms related to plague and antimicrobials. Articles were included if they contained 1) a group of patients treated for plague, with outcomes reported by antimicrobial regimen, and 2) laboratory evidence of Y. pestis infection or an epidemiologic link to patients with laboratory evidence of Y. pestis. Case fatality rate by antimicrobial regimen was calculated. RESULTS: In total, 5837 articles were identified; among these, 26 articles published between 1939 and 2008 met inclusion criteria. A total of 2631 cases of human plague reported within these articles were included. Among cases classified by primary clinical form of plague, 93.6% were bubonic, 5.9% pneumonic, and 0.5% septicemic with associated case fatalities of 14.2%, 31.1%, and 20.0%, respectively. Case fatality rate among patients who received monotherapy with tetracyclines, chloramphenicol, aminoglycosides, or sulfonamides was 1.3%, 1.4%, 7.5%, and 20.2%, respectively. Fluoroquinolones were only given as part of combination therapy. Penicillin was associated with a case fatality rate of 75%. CONCLUSIONS: Tetracyclines, chloramphenicol, and aminoglycosides were associated with the lowest case fatality rates of all antimicrobials used for treatment of plague. Additional research is needed to determine the efficacy of fluoroquinolones as monotherapy.

Antimicrobial Treatment of Human Plague: A Systematic Review of the Literature on Individual Cases, 1937-2019.

BACKGROUND: Yersinia pestis remains endemic in Africa, Asia, and the Americas and is a known bioterrorism agent. Treatment with aminoglycosides such as streptomycin or gentamicin is effective when initiated early in illness but can have serious side effects. Alternatives such as fluoroquinolones, tetracyclines, and sulfonamides are potentially safer but lack robust human data on efficacy. METHODS: We searched PubMed Central, Medline, Embase, and other databases for articles in any language with terms related to plague and antimicrobials. Articles that contained case-level information on antimicrobial treatment and patient outcome were included. We abstracted information related to patient demographics, clinical features, treatment, and fatality. RESULTS: Among 5837 articles screened, we found 762 published cases of treated plague reported from 1937 to 2019. Fifty-nine percent were male; median age was 22 years (range, 8 days-80 years). The case fatality rate was 20% overall. Most patients had primary bubonic (63%), pneumonic (21%), or septicemic (5%) plague, with associated case fatality rates of 17%, 27%, and 38%, respectively. Among those treated with an aminoglycoside (n = 407 [53%]), the case fatality rate was 13%. Among those treated with a sulfonamide (n = 322 [42%]), tetracycline (n = 171 [22%]), or fluoroquinolone (n = 61 [8%]), fatality was 23%, 10%, and 12%, respectively. Case fatality rate did not substantially differ between patients treated with 1 vs 2 classes of antimicrobials considered to be effective for plague. CONCLUSIONS: In addition to aminoglycosides, other classes of antimicrobials including tetracyclines, fluoroquinolones, and sulfonamides are effective for plague treatment, although publication bias and low numbers in certain treatment groups may limit interpretation.